Cellular interactions in the generation of cytolytic T lymphocyte responses. Analysis of the helper T cell pathway.

Murine splenic lymphocytes exhibit a requirement for helper T cells for the induction of a cytolytic T lymphocyte response to suboptimal doses of allogeneic cells, membranes from allogeneic cells, or purified H-2 antigen in liposomes. The conditions where a requirement for help is apparent are the same conditions where a dependence on splenic adherent cells (SAC) has been demonstrated (Weinberger, O. et al., PROC. Natl. Acad, Sci, USA 1980. 77: 6091). Help can be provided in the form of primed, radioresistant, Ly-1+ spleen or lymph node cells or helper factor (interleukin 2, IL-2). A factor generated from phytohemagglutinin-stimulated human lymphocytes, when added to culture in the presence of antigen, bypassed the requirement for Ia+ SAC and helper cells. IL-2 reconstituted the response to H-2K(k) in liposomes in cultures depleted of SAC, strongly suggesting that the helper cell must see antigen re-expressed by an antigen-presenting cell, whereas the prekiller does not. IL-2 could be generated by culturing Ly-1+ murine spleen cells with H-2K(k) pulsed on SAC.